Réaction #634657

Équation de réaction

hydrogen

NaH

1-[2-(1H-indol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one

cesium carbonate

→

2

Rendement 35.9%

2,2-Dimethyl-1-[2-(2-pyrrolidin-1-yl-pyridin-4-yl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one

Rendement 35.9%

Solvants

toluene acetone

acetonitrile

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGwas stirred at 130° C. under microwave irradiation for two hours
3. 3
   Températurebefore being cooled to RT
4. 4
   AutreThe reaction mixture was partitioned between EtOAc and saturated aqueous ammonium chloride
5. 5
   Extractionthe aqueous layer was back extracted twice with EtOAc
6. 6
   SéchageCombined organic layers were dried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Autreevaporated
9. 9
   AutreThe residue was purified by SiO2 chromatography (hexanes/EtOAc 0-20% EtOAc)

Mode opératoire

Step 2—A mixture of 1-[2-(1H-indol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (0.2 g, 0.446 mmol), 1 (0.23 g, 0.892 mmol), and cesium carbonate (0.29 g, 0.892 mmol) in 4 mL of acetonitrile was stirred at 80° C. overnight. TLC (hexanes/EtOAc 7/3) showed little conversion, so NaH 60% dispersion in oil (0.067 g, 1.672 mmol) was added and the after hydrogen evolution had stopped the reaction mixture was stirred at 130° C. under microwave irradiation for two hours before being cooled to RT. The reaction mixture was partitioned between EtOAc and saturated aqueous ammonium chloride, the aqueous layer was back extracted twice with EtOAc. Combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified by SiO2 chromatography (hexanes/EtOAc 0-20% EtOAc) and then a second time (toluene/acetone 0-10% acetone) to give 0.028 g of 2 (10% yield)

Source